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Medicine May 2019It is commonly reported a limitation of therapeutic strategy in Eisenmenger syndrome (ES) historically. This qualitative systematic review is conducted to evaluate the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It is commonly reported a limitation of therapeutic strategy in Eisenmenger syndrome (ES) historically. This qualitative systematic review is conducted to evaluate the safety and efficacy of pulmonary arterial hypertension-specific drug therapy (PAH-SDT) for ES patients for a clinical therapeutic strategy based on evidence.
METHODS
PubMed, EMBASE, and the Cochrane Library databases have been systematically reviewed up to January 2019. Two reviewers independently conducted a literature search, quality evaluation, and data extraction. The occurrence of death, deterioration, and adverse events (AEs) has respectively been described as a count or percentage. Meta-analysis was conducted by Stata 15.1, and weighted mean differences (WMD) with 95% confidence intervals (CI) were recorded for continuous data. Randomized-effect model or fixed-effect model was applied according to the heterogeneity test.
RESULTS
Fifteen citations recruiting 456 patients associated with ES were eventually pooled, which involved 4 RCTs, 6 prospective studies, and 5 retrospective studies. Within the first year, it indicated PAH-SDT significantly ameliorated exercise capacity in 6-minute walk distance (6MWD) (I = 60.5%; WMD: 53.86 m, 95% CI [36.59, 71.13], P < .001), functional class (FC) (WMD = -0.71, 95% CI [-0.98, -0.44], P < .001) and Borg dyspnea index (WMD = -1.28, 95% CI [-1.86, -0.70], P < .001), in addition to hemodynamics, especially mean pulmonary arterial pressure by 5.70 mmHg (WMD = -5.70 mmHg, 95% CI [-8.19, -3.22], P < .001) and pulmonary vascular resistance by 4.20 wood U (WMD: -4.20, 95% CI [-7.32, -1.09], P = .008), but unsatisfactory effects in oxygen saturation at exercise (P = .747). In a prolonged medication, bosentan, a dual ERA, has been proved acting an important role in improving exercise tolerance of patients with ES (6MWD: I = 47.5%; WMD: 88.68 m, 95% CI [54.05, 123.3], P < .001; FC: I = 0.0%; WMD = -0.65, 95% CI [-1.10, -0.19], P = .006). While a nonsignificant change of 6MWD was noted in a long-term therapy of ambrisentan (P = .385). There existed rare evidence about the efficacy and safety of macitentan, phosphodiesterase-5 inhibitors (PDE5i), and prostanoids in a prolonged medication. Most AEs were recorded as mild to moderate with PAH-SDT, but about 4.3% individuals treated with endothelin receptor antagonists (ERAs) suffered from serious ones, and 3.9% suffered from death.
CONCLUSIONS
This systematic review and meta-analysis proved PAH-SDT as a safe and effective role in ES in an early stage. However, in a long-term treatment, bosentan has been supported for a lasting effect on exercise tolerance. A further multicenter research with a large sample about pharmacotherapy of ES is necessary.
Topics: Antihypertensive Agents; Bosentan; Eisenmenger Complex; Endothelin Receptor Antagonists; Exercise Tolerance; Hemodynamics; Humans; Hypertension, Pulmonary; Oxygen; Phenylpropionates; Phosphodiesterase 5 Inhibitors; Prostaglandins; Pyridazines; Pyrimidines; Sulfonamides
PubMed: 31096477
DOI: 10.1097/MD.0000000000015632 -
Annales de Dermatologie Et de... Mar 2011Pemphigus is a rare autoimmune bullous disorder. Numerous treatment regimens have been proposed in the literature. (Review)
Review
BACKGROUND
Pemphigus is a rare autoimmune bullous disorder. Numerous treatment regimens have been proposed in the literature.
OBJECTIVE
To assess the efficacy and tolerance of treatment regimens proposed in pemphigus vulgaris (PV) and pemphigus foliaceus (PF), from a systematic review of the literature.
METHODS
Randomized control trials have been identified using the PubMed and Embase databases up to April 2009. Uncontrolled prospective and retrospective studies have also been analyzed.
RESULTS
Eleven randomized control trials having included a total number of 421 patients (377 PV, 44 PF) have been analyzed. Most studies had a limited statistical power due to the rather low number of cases included. Results from ten different treatment regimens have been analyzed: different dosages of prednisone and prednisolone, pulse intravenous dexamethasone, azathioprine, cyclophosphamide, cyclosporine, dapsone, mycophenolate mofetil, plasmapheresis, topical applications of epidermal growth factor (EGF), and intravenous immune globulins (IVIG). Inclusion criteria were: (i) consecutive patients in nine studies, (ii) patients who did not respond to low doses of corticosteroids in one study, and (iii) patients with relapsing type of pemphigus in one study. None of these studies allowed identifying the best effective and well tolerated regimen. Mycophenolate mofetil was more effective than azathioprine for disease control (from one study; n=40; OR=0.72; 95% CI=0.52-0.99). However, no difference in the rate of clinical remission was evidenced between these drugs. Azathioprine and cyclophosphamide seem to have a corticosteroid sparing effect.
CONCLUSION
Data from the literature did not allow identifying the best therapeutic regimen, mainly because of the lack of statistical power of most studies. The usefulness of immunosuppressant added to systemic corticosteroids as the first line of treatment is not clearly established.
Topics: Adrenal Cortex Hormones; Combined Modality Therapy; Drug Therapy, Combination; Epidermal Growth Factor; Gold Compounds; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Meta-Analysis as Topic; Multicenter Studies as Topic; Niacinamide; Paraneoplastic Syndromes; Pemphigus; Plasma Exchange; Prospective Studies; Randomized Controlled Trials as Topic; Recurrence; Retrospective Studies; Tetracycline
PubMed: 21397148
DOI: 10.1016/j.annder.2011.01.016 -
Clinical Therapeutics Jun 2012Epidemiologic studies have revealed that postprandial hyperglycemia significantly contributes to high glycated hemoglobin concentrations and could be linked to the... (Review)
Review
BACKGROUND
Epidemiologic studies have revealed that postprandial hyperglycemia significantly contributes to high glycated hemoglobin concentrations and could be linked to the development of chronic diabetic complications.
OBJECTIVE
The purpose of our review was to evaluate the clinical efficacy and safety profile of treatment with acarbose alone and combined with other antidiabetic drugs.
METHODS
A systematic search strategy was developed to identify randomized controlled trials included in MEDLINE and the Cochrane Register of Controlled Trials. The terms acarbose, α-glucosidase inhibitors, type 2 diabetes, adverse events, combination therapy, and postprandial glucose were incorporated into an electronic search strategy that included the Dickersin filter for randomized controlled trials. To qualify for inclusion, clinical trials had to be randomized trials comparing treatment with acarbose at any dosage with any other antidiabetic drug in patients with type 2 diabetes mellitus or impaired glucose tolerance. Eligible trials had to present results on glycemic control or adverse events. Trial participants needed to be affected by type 2 diabetes mellitus or have impaired glucose tolerance, and the intervention had to include acarbose at any dosage as monotherapy or combined with other antidiabetic drugs. A validated 3-item scale was used to evaluate the overall reporting quality of the trials selected for inclusion in the present review. Nineteen trials were included.
RESULTS
Treatment with acarbose significantly reduced glycated hemoglobin levels when given as monotherapy and as an add-on to other antidiabetic drug treatment (P < 0.0001). Acarbose treatment was effective in patients with uncontrolled type 2 diabetes and in patients with apparently good metabolic control owing to its positive effect on postprandial hyperglycemia (P < 0.0001). Treatment with acarbose seemed to improve the lipid profile (P < 0.05), reduce circulating levels of cell adhesion molecules (P < 0.05), reduce intima-media thickness progression (P = 0.01), and reverse impaired glucose tolerance to normal glucose tolerance (P < 0.0001).
CONCLUSIONS
When current therapy is not adequate to obtain glycemic control, acarbose could be an option as monotherapy and as an add-on to other antidiabetic drug treatment, especially when postprandial hyperglycemia is the main concern. Long-term studies are needed to determine whether the effects observed with acarbose use are maintained over the years.
Topics: Acarbose; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Placebos; Randomized Controlled Trials as Topic
PubMed: 22560622
DOI: 10.1016/j.clinthera.2012.04.012 -
The Cochrane Database of Systematic... Jun 2010Phenylketonuria results from a deficiency of the enzyme phenylalanine hydroxylase. Dietary restriction of phenylalanine keeps blood phenylalanine concentration low. Most... (Review)
Review
BACKGROUND
Phenylketonuria results from a deficiency of the enzyme phenylalanine hydroxylase. Dietary restriction of phenylalanine keeps blood phenylalanine concentration low. Most natural foods are excluded from diet and supplements are used to supply other nutrients. Recent publications report a decrease in blood phenylalanine concentration in some patients treated with sapropterin dihydrochloride. We examined the evidence for the use of sapropterin dihydrochloride to treat phenylketonuria.
OBJECTIVES
To assess the safety and efficacy of sapropterin dihydrochloride in lowering blood phenylalanine concentration in people with phenylketonuria.
SEARCH STRATEGY
We identified relevant trials from the Group's Inborn Errors of Metabolism Trials Register. Last search:07 May 2010.We also searched ClinicalTrials.gov and Current controlled trials. Last search: 01 September 2009.We contacted the manufacturers of the drug (BioMarin Pharmaceutical Inc.) for information regarding any unpublished trials.
SELECTION CRITERIA
Randomized controlled trials comparing sapropterin with no supplementation or placebo in people with phenylketonuria due to phenylalanine hydroxylase deficiency.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trials and extracted outcome data.
MAIN RESULTS
Two placebo-controlled trials were included. One trial administered 10 mg/kg/day sapropterin in 89 children and adults with phenylketonuria whose diets were not restricted and who had previously responded to saproterin.This trial measured change in blood phenylalanine concentration. The second trial screened 90 children (4 to 12 years) with phenylketonuria whose diet was restricted, for responsiveness to sapropterin. Forty-six responders entered the placebo-controlled part of the trial and received 20 mg/kg/day sapropterin. This trial measured change in both phenylalanine concentration and protein tolerance. Both trials reported adverse events. The trials showed an overall low risk of bias; but both are Biomarin-sponsored. One trial showed a significant lowering in blood phenylalanine concentration in the sapropterin group (10 mg/kg/day), mean difference -238.80 mumol/L (95% confidence interval -343.09 to -134.51); a second trial (20 mg/kg/day sapropterin) showed a non-significant difference, mean difference -51.90 mumol/L (95% confidence interval -197.27 to 93.47). The second trial also reported a significant increase in phenylalanine tolerance, mean difference18.00 mg/kg/day (95% confidence interval 12.28 to 23.72) in the 20 mg/kg/day sapropterin group.
AUTHORS' CONCLUSIONS
There is evidence of short-term benefit from using sapropterin in some patients with sapropterin-responsive forms of phenylketonuria; blood phenylalanine concentration is lowered and protein tolerance increased. There are no serious adverse events associated with using sapropterin in the short term.There is no evidence on the long-term effects of sapropterin and no clear evidence of effectiveness in severe phenylketonuria.
Topics: Adult; Biopterins; Child; Humans; Phenylalanine; Phenylketonurias
PubMed: 20556789
DOI: 10.1002/14651858.CD008005.pub2 -
Critical Reviews in Oncology/hematology Dec 2023The advent of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) has been transformative for the treatment of advanced renal cell carcinoma (RCC).... (Review)
Review
The advent of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) has been transformative for the treatment of advanced renal cell carcinoma (RCC). Their efficacy post-surgical resection remains a contentious point. Various phase 3 RCTs have assessed their potency. Amongst evaluated agents, sunitinib and pembrolizumab have demonstrated notable disease-free survival benefits. Sunitinib's potential is diminished due to absence of clear overall survival (OS) benefits and side-effect profile. Pembrolizumab shows better tolerance, conclusive OS data are forthcoming. This scenario underscores the pressing need for advanced risk stratification methods and discovery of novel biomarkers. Existing strategies, largely pre-dating TKI and ICI therapeutic era, lack sufficient accuracy in predicting relapse-risk. Our review offers a comprehensive analysis of key phase 3 RCTs, focusing on TKIs, mTOR-inhibitors, and ICIs for adjuvant RCC treatment. The intent is to shed light on the intricate landscape of RCC treatment, guiding future research directions for optimizing patient outcomes.
Topics: Humans; Carcinoma, Renal Cell; Sunitinib; Kidney Neoplasms; Neoplasm Recurrence, Local; Disease-Free Survival
PubMed: 37748694
DOI: 10.1016/j.critrevonc.2023.104144 -
The Journal of Clinical Psychiatry Jul 2023Aiming at revising the therapeutic reference range for olanzapine, the present study highlights the association between blood olanzapine levels, clinical effects, and...
Aiming at revising the therapeutic reference range for olanzapine, the present study highlights the association between blood olanzapine levels, clinical effects, and dopamine D-receptor occupancy for oral and long-acting injectable (LAI) formulations. Databases were systematically searched for randomized controlled trials (RCTs) and uncontrolled trials concerning blood olanzapine levels in relation to clinical outcomes or D-receptor occupancy using MEDLINE (PubMed), Web of Science, PsycINFO, and Cochrane Library (March 2021, updated in December 2021). We excluded articles not written in English or German and non-human data. Search terms included , , , , and . The process of study selection followed a previously published protocol and PRISMA guidelines. A total of 2,824 articles were identified through database search and 1 article via reference list check. Thirty-four studies were suitable for qualitative synthesis, and 13 studies were included in the quantitative analysis. Reviewers performed data extraction and quality assessment of the included studies independently following the review protocol. Evidence for a relationship between blood olanzapine level and efficacy/side effects (constipation) is considered low (Level C). In total, 3 studies of moderate quality consistently showed therapeutic thresholds of around 20 ng/mL for olanzapine 12 hours post-dose. This threshold is in line with findings from positron emission tomography (PET) studies that suggest optimal drug efficacy (65%-80% D-receptor occupancy) between 17 and 44 ng/mL. We suggest a therapeutic reference range of 20-40 ng/mL for olanzapine oral and LAI formulations. In this range, optimal treatment response is expected in patients with schizophrenia and schizophrenia spectrum disorders. Side effects, especially weight gain, may already occur at therapeutic levels. However, higher plasma concentrations are in general well tolerated and should not necessarily require a dose reduction in case of good response and tolerance.
Topics: Humans; Olanzapine; Antipsychotic Agents; Reference Values; Schizophrenia; Receptors, Dopamine D2; Benzodiazepines
PubMed: 37471567
DOI: 10.4088/JCP.22r14626 -
Journal of Psychiatric Research Apr 2021Dimenhydrinate (DMH) is an antihistamine used to treat nausea and vomiting. Although widely available in pharmacies as an over the counter medication, there have been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dimenhydrinate (DMH) is an antihistamine used to treat nausea and vomiting. Although widely available in pharmacies as an over the counter medication, there have been reports of potential DMH tolerance and dependence and a possible euphoric potential accompanying heavy use (>100 mg/day). Despite the potential for misuse, there is a gap in the literature concerning patterns, characteristics, and potential mechanisms of DMH misuse.
AIMS
This review aimed to synthesize evidence on the pharmacology, clinical effects, and management of DMH misuse and dependence to inform clinical decision making and relevant drug policy.
METHODS
We conducted a systematic review in accordance with the PRISMA guidelines and using Cochrane collaboration methods. We searched seven databases from their inception through July 2019. To be included in the review, studies needed to measure or focus on one or more dimensions of morbidity or mortality related to the misuse of DMH. Quantitative, qualitative and mixed-method studies were included in order to capture the breadth of possible studies. Studies were excluded if they did not fit into the conceptual framework of the study of if they focused primarily on the misuse of other substances. A narrative synthesis of study findings was pursued given the limited capacity for a quantitative meta-analysis.
FINDINGS
We identified 24 studies, which described a range of neuropsychiatric sequelae related to DMH consumption, including seizures, psychosis, depression, intoxication (resembling anticholinergic syndrome) and withdrawal. The sedative and euphoric properties, readily available nature, and low cost of DMH appear to facilitate DMH dependence, which were more commonly reported among individuals who had concurrent psychiatric disorders, displaying symptoms such as low motivation, poor concentration, and delirium. The overall quality of studies identified by this review was low-largely because the majority of studies were case reports or review articles, with few intervention or cohort studies.
CONCLUSIONS
There is some evidence to suggest the existence of DMH-related syndromes involving intoxication, withdrawal, and dependence, more commonly among long-term, heavy DMH consumers. However, higher quality studies are needed to confirm preliminary findings that there may be a biological basis for such syndromes.
Topics: Dimenhydrinate; Humans; Psychotic Disorders
PubMed: 33153760
DOI: 10.1016/j.jpsychires.2020.10.032 -
Journal of Thoracic Disease Nov 2023The role of combination treatments with two antifibrotic agents, pirfenidone and nintedanib, has been not established in idiopathic pulmonary fibrosis (IPF). This study...
BACKGROUND
The role of combination treatments with two antifibrotic agents, pirfenidone and nintedanib, has been not established in idiopathic pulmonary fibrosis (IPF). This study was performed to investigate the safety and tolerability of combination antifibrotic treatment in patients with IPF.
METHODS
We conducted a proportional meta-analysis and searched PubMed, EMBASE, and the Cochrane Central Register for relevant clinical trials. The primary outcome was the proportion of discontinuation of combination treatment over the treatment period. We also examined the pooled proportions of serious and any adverse drug reactions (ADRs).
RESULTS
Four clinical trials involving 191 patients were analyzed. In pooled estimates, 29% of patients discontinued treatment during the study period [95% confidence interval (CI): 17-41%, I=65.42%]. The pooled proportions of serious and any ADRs were 10% (95% CI: 1-19%; I=79.13%) and 82% (95% CI: 75-90%; I=39.20%), respectively. During the follow-up period, gastrointestinal symptoms were the most frequent ADR. Acute exacerbation (AE) of IPF was reported in 7.0% of patients.
CONCLUSIONS
Our findings showed relatively frequent incidence of discontinuation and ADRs for combination therapy in IPF. Further large-scale, randomized, controlled trials are needed to support our results because of the methodological limitations of the included trials and a scarcity of trials for analysis.
PubMed: 38090320
DOI: 10.21037/jtd-23-946 -
Journal of Alternative and... Jul 2018To assess the effectiveness and safety of Traditional Chinese patent medicines (TCPMs) for managing impaired glucose tolerance (IGT). (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION/AIM
To assess the effectiveness and safety of Traditional Chinese patent medicines (TCPMs) for managing impaired glucose tolerance (IGT).
METHODS
Seven databases were searched to identify eligible trials published from incepting to May 1, 2016. Randomized controlled trials (RCTs) involving TCPM for IGT with a minimum follow-up duration of 6 months were included for analysis. Data extraction and quality assessment were performed by two reviewers independently. Data synthesis was analyzed using Review Manager 5.3 software. Subgroup analysis was carried out to assess the robustness of results of meta-analysis.
RESULTS
Eighteen trials with a total of 3172 participants met the inclusion criteria. The methodological quality of the RCTs was variable. Comparing with receiving lifestyle modification (LM) alone, TCPM plus LM was significantly better at reducing the incidence of diabetes (risk ratio [RR] 0.45; 95% confidence interval [CI] 0.36-0.57, p < 0.00001) and normalizing the blood glucose (RR 0.72; 95% CI 0.64-0.82, p < 0.00001). TCPM plus LM was superior in decreasing the levels of 2hPG, body mass index (BMI), fasting insulin, and 2 h insulin compared with LM alone (2hPG: mean difference [MD] -1.13; 95% CI -1.68 to -0.58, p < 0.0001; BMI: MD -0.42; 95% CI -0.71 to -0.14, p = 0.004; fasting insulin: MD -2.44; 95% CI -3.79 to -1.09, p = 0.0004; and 2 h insulin: MD -8.26; 95% CI -8.47 to -8.05, p < 0.00001). Compared with placebo plus LM, TCPM plus LM was superior in reducing diabetes (RR 0.54; 95% CI 0.42-0.69, p < 0.00001) and normalizing blood glucose (RR 0.55; 95% CI 0.41-0.73, p < 0.00001; the interventions were also associated with a decline in the two-hour postprandial blood glucose (2hPG) levels (MD -1.45; 95% CI -2.11 to -0.79, p < 0.0001) and BMI levels (MD -1.12; 95% CI -2.00 to -0.24, p < 0.0001). There were no significant differences in adverse events between two groups. Subgroup analysis found no significant difference in overall effects among all study characteristics, indicating that the overall effects were stable.
CONCLUSIONS
The study indicated that TCPM combined with moderate lifestyle modification had significant effect on IGT. Further studies are needed to provide more reliable evidence. The PROSPERO registration is No. CRD42016039312.
Topics: Adult; Aged; Aged, 80 and over; Drugs, Chinese Herbal; Female; Glucose Intolerance; Humans; Male; Medicine, Chinese Traditional; Middle Aged; Randomized Controlled Trials as Topic; Young Adult
PubMed: 29624416
DOI: 10.1089/acm.2017.0302 -
The Patient Jun 2018Stated-preference methods have been widely used to evaluate patient-relative preferences for the benefits and potential harms of psoriasis treatments. However, risk... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Stated-preference methods have been widely used to evaluate patient-relative preferences for the benefits and potential harms of psoriasis treatments. However, risk tolerance measures for treatment-related harms, a corollary of preferences, are rare despite their critical role in shared decision making and regulatory benefit-risk evaluations. This article presents a method to enhance information on patient risk tolerance through previously published preference results.
OBJECTIVE
The objective of this article was to conduct the first meta-analysis of preferences to characterize the distribution of patients' maximum acceptable risk of harms associated with psoriasis treatments.
DATA SOURCES
Maximum acceptable risks for treatment-related adverse events were extracted or derived from preference results published between 2011 and 2017.
SYNTHESIS METHODS
Four different analyses were conducted to evaluate maximum acceptable risk information across studies: (1) listing of maximum acceptable risk values, (2) naïve aggregation of maximum acceptable risks, (3) estimation of maximum acceptable risk mother distribution, and (4) random-effect regression analysis of maximum acceptable risks.
RESULTS
Nine publications with maximum acceptable risk results, or with enough information to derive maximum acceptable risks, were identified from the search and screening of preference studies. The most commonly evaluated treatment benefits were duration of benefits, percentage and probability of improvement, and reductions in the coverage of lesions. The adverse-event risks most often included in the publications were those commonly associated with biologics, such as serious infections and malignancies. As expected, maximum acceptable risks changed with treatment benefits and treatment-related adverse events.
CONCLUSIONS
The results confirm the feasibility of using previously published preference information to characterize patient risk tolerance. The estimated distributions of maximum acceptable risk provide a benchmark against which future results can be compared, and signal gaps in our understanding of risk tolerance for specific health outcomes.
Topics: Adult; Aged; Aged, 80 and over; Decision Making; Dermatologic Agents; Female; Humans; Male; Middle Aged; Patient Preference; Psoriasis; Risk Assessment
PubMed: 29332301
DOI: 10.1007/s40271-017-0295-z